Pilot Study of the Utility of Empiric Antibiotic Therapy for Suspected ICU-Acquired Infection

NCT00438269 | Completed Phase 2

• 1 other identifier: AATICC Pilot Study
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Infection developing in the intensive care unit is a common complication of critical illness, but notoriously difficult to diagnose. A definite diagnosis based on the most reliable tests usually is not possible for at least two days. It is unclear what the optimal management approach should be while awaiting the results of diagnostic tests. In some circumstances, broad spectrum antibiotics are started with a plan to adjust them once the results of cultures are available. Observational studies show that this results in greater antibiotic use, and the risk of superinfection and resistance. In other circumstances, antibiotics may be withheld pending the results of cultures, a strategy that leads to a delay in therapy when cultures are positive, and that may be associated with a worse clinical outcome. We undertook a randomized pilot study to address the question: "In a critically ill patient for whom clinicians are uncertain whether infection may be present, and in whom potential sites of infection have been managed by removing or changing invasive devices, can a policy of delaying antibiotic treatment until cultures are available reduce the risks of excessive antibiotic use, without increasing the risks associated with delayed therapy?" Recognizing that the question has not been formally addressed before, and that approaches to clinical management are both widely divergent and passionately held, our pilot study tested the feasibility and acceptability of undertaking a larger trial with sufficient power to determine equivalence.

Conditions

Nosocomial Infection; Pneumonia; Systemic Inflammatory Response Syndrome; Critical Illness; Pyrexia

Keywords

Infection; Empiric; Antibiotics; Nosocomial; Pyrexia; Leukocytosis; Resistance

Outcome Measures

Primary Outcomes (2)

• Feasibility: = % of eligible patients who were consented and randomized

• Acceptability: = % of patients in each study arm who were switched to open label therapy prior to culture results

Secondary Outcomes (5)

• Mortality (14, 30, 90 day)

• Microbial resistance patterns

• ICU-free days

• Antibiotic-free days

• Change in organ dysfunction (MOD scores)

Interventions

Site-specific empiric regimens included: Meropenem DRUG

Piperacillin/tazobactam DRUG

Ciprofloxacin and cefazolin +/- metronidazole DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In hospital \> 72 hrs and in ICU \> 24hrs, and
• Core temperature ≥38.5°C, or temperature ≥ 38.0°C with a WBC\>12,000/mm3, or temperature ≤ 36.0°C with a WBC \> 12,000/mm3
• Suspicion of infection

You may not qualify if:

• Age \< 18 years
• Imminent death (within 24 hrs) or withdrawal of aggressive therapy
• Prosthetic heart valve or vascular graft
• Neutropenia (Absolute neutrophil count \< 1000/mm3)
• Received \> 16 hours of a broad spectrum antibiotic in the last 24 hours (3rd gen cephalosporin, fluoroquinolone, carbapenem, anti-pseudomonal penicillin) or any combination therapy
• History of allergic reaction to both study medications
• New physical findings consistent with infection:
• Meningeal signs
• Peritonitis + free air on Abdo x-ray
• Soft tissue infection / cellulitis
• Murmur \& suspicion of endocarditis
• Newly available (within past 24 hours) culture results consistent with infection

Sponsors & Collaborators

• Canadian Critical Care Trials Group: lead
• The Physicians' Services Incorporated Foundation: collaborator

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

MeSH Terms

Conditions

Cross Infection; Pneumonia; Systemic Inflammatory Response Syndrome; Critical Illness; Fever; Infections; Leukocytosis

Interventions

Piperacillin, Tazobactam Drug Combination; Ciprofloxacin

Condition Hierarchy (Ancestors)

Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Inflammation; Shock; Body Temperature Changes; Signs and Symptoms; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Tazobactam; Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Piperacillin; Ampicillin; Penicillin G; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Officials

• Mary-Anne W Aarts, MD MSc

  University of Toronto

  PRINCIPAL INVESTIGATOR

• John C Marshall, MD

  University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 17, 2007
• First Posted: February 22, 2007
• Study Start: February 1, 2003
• Study Completion: March 1, 2005
• Last Updated: February 22, 2007

Record last verified: 2007-02

Locations

CA (1)